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Epigenetic reprogramming of UDP‐N‐acetylglucosamine 2‐ epimerase/N‐acetylmannosamine kinase (GNE) in HIV‐1‐ infected CEM T cells
Author(s) -
Giordanengo Valérie,
Ollier Laurence,
Lanteri Marion,
Lesimple Josette,
March Denise,
Thyss Sylvain,
Lefebvre JeanClaude
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2467fje
Subject(s) - sialic acid , glycoconjugate , biology , microvesicles , kinase , microbiology and biotechnology , reprogramming , chemistry , gene , biochemistry , microrna
Sialylated glycoconjugates mediate several key lymphocyte functions. We previously reported that hyposialylation occurred in latently HIV‐1‐infected CEM T cells, despite the fully preserved catalytic activity of several sialyltransferases. We show now that these cells are affected by a down‐regulation of UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (GNE), which leads to a dramatic decrease in the synthesis of CMP‐sialic acid, the donor substrate of all sialyltransferases. The GNE gene promoter was found to be located in a CpG island with several regulatory motifs CREB, SP1, and AP‐2. De novo hypermethylation of this promoter was observed in HIV‐1‐infected CEM cells. This phenomenon might explain some immunological disorders that persist in infected individuals despite long‐term therapeutically controlled viral replication. Indeed, an overall decrease in sialic acid engraftment can affect glycoproteins, notably those in which the sialylation status is crucial to ensure homing, recirculation, and survival of lymphocytes.